By Carrie St. Michel – Published in USC Norris Cancer Report Fall 2013 Once tumors have spread to their lymph nodes, patients with cervical cancer face tough odds. But research in the treatment of skin cancer may hold the key to a brighter future for these patients. “At this point, we don’t have anything to offer them other than chemoradiation, and that hasn’t changed since 1999,” says Yvonne Lin, MD, assistant professor of obstetrics and gynecology at the Keck School of Medicine of USC. While chemoradiation is 92 percent curative for localized cervical cancer (based on five-year survival rates), outcomes plummet when the disease spreads outside the cervix. “With patients who have lymph node involvement, there’s a strong chance of cancer recurrence within the first two years following treatment,” says Lin, who is a leading member of USC Norris Comprehensive Cancer Center’s Women’s Cancer Program. Lin learned that grim fact firsthand while caring for cervical cancer patients at Los Angeles County-USC Medical Center. “This is a population that often doesn’t have access to screening tests or to the HPV vaccine, so you see a lot of advanced-stage cervical cancer,” Lin says. [Most cervical cancer is caused by the human papilloma virus (HPV) infecting cervical-cells; a Pap test screens for cervical-cell abnormalities.] Lin knew that even if those patients had the best standard of care, their cancer was unlikely to be defeated, so she began thinking of different ways to treat them. “Isn’t there some type of additional treatment we can offer to prevent this high rate of recurrence?” Lin’s thoughts then turned to an even fiercer type of cancer-metastatic melanoma. This most deadly form of skin cancer captured Lin’s attention because two Phase III clinical trials testing the drug ipilimumab had shown significant improvement in overall survival. Approved by the Food and Drug Administration in 2011, the drug is designed to manipulate the immune system. “Instead of allowing the immune system to turn off, ipilimumab keeps the immune system in a revved-up state,” Lin says. “I use the analogy of a gas pedal and a brake pedal. Ipilimumab removes the immune system’s brakes. If a patient’s immune response is allowed to perpetuate, then the patient can have clearance of cancer cells.” Lin saw a good fit between ipilimumab and cervical cancer. “Cervical cancer is a virally driven disease through HPV, and we know that HPV has a specific antigen that should launch an immune response,” she says. Connecting the dots, Lin concluded that “cervical cancer was the most appropriate next disease site for testing ipilimumab.” Lin thus became the chair of a multi-center, national clinical trial that is determining the efficacy of fighting cervical cancer. The nationwide trial, which is funded by the National Cancer Institute’s Gynecological Oncology Group and the USC Norris Auxiliary Endowment, is currently enrolling women newly diagnosed with locally advanced cervical cancer with lymph-node involvement. Trial participants will receive chemoradiation over the course of eight weeks, followed by intravenous ipilimumabevery three weeks, for 12 weeks. Throughout the trial, Lin and her team will take a series of scientific snapshots. “No one really knows if every patient’s immune system turns on, and, if it does, how long it stays on,” she says. “So we’ll be painting the landscape of the immune system at different points in time, with an eye toward answering the question: Did patients whose immune systems turned on have a more robust response to this immune therapy?” If ipilimumab is proven to be safe and tolerable, the next steps would be Phase II and Phase III clinical trials. Lin’s long-term sights are set on the ultimate translational endpoint: “If the immune system can be harnessed against cervical cancer, then we can offer women a new standard of care.”